ArticleCardiovascular research2013
Super-resolution fluorescence microscopy of the cardiac connexome reveals plakophilin-2 inside the connexin43 plaque.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exercise-induced dysregulation of the adrenergic response in a mouse model of PKP2-arrhythmogenic cardiomyopathy.Heart rhythm · 2025Article
- Comprehensive analysis of desmosomal protein remodelling identifies desmocollin-2 as potential biomarker for arrhythmogenic cardiomyopathy.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.Journal of cell science · 2025Article
- Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit.eLife · 2024Article
- Review
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes.Computational and structural biotechnology journal · 2023Article
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- Desmosomes: emerging pathways and non-canonical functions in cardiac arrhythmias and disease.Biophysical reviews · 2021Review
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Super-resolution mapping of cellular double-strand break resection complexes during homologous recombination.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease.Cell stem cell · 2020Article
- Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.Human molecular genetics · 2020Article
- Ankyrin-G mediates targeting of both NaeLife · 2020Article
- Genetic Animal Models for Arrhythmogenic Cardiomyopathy.Frontiers in physiology · 2020Review
- Molecular mechanisms of arrhythmogenic cardiomyopathy.Nature reviews. Cardiology · 2019Review
- Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration?International journal of molecular sciences · 2019Review
- Desmosomes: Essential contributors to an integrated intercellular junction network.F1000Research · 2019Review
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Authors and funding
7 authors.
Funding
Abstract
aimsCell function requires formation of molecular clusters localized to discrete subdomains. The composition of these interactomes, and their spatial organization, cannot be discerned by conventional microscopy given the resolution constraints imposed by the diffraction limit of light (∼200-300 nm). Our aims were (i) Implement single-molecule imaging and analysis tools to resolve the nano-scale architecture of cardiac myocytes. (ii) Using these tools, to map two molecules classically defined as components 'of the desmosome' and 'of the gap junction', and defined their spatial organization. METHODS AND
resultsWe built a set-up on a conventional inverted microscope using commercially available optics. Laser illumination, reducing, and oxygen scavenging conditions were used to manipulate the blinking behaviour of individual fluorescent reporters. Movies of blinking fluorophores were reconstructed to generate subdiffraction images at ∼20 nm resolution. With this method, we characterized clusters of connexin43 (Cx43) and of 'the desmosomal protein' plakophilin-2 (PKP2). In about half of Cx43 clusters, we observed overlay of Cx43 and PKP2 at the Cx43 plaque edge. SiRNA-mediated loss of Ankyrin-G expression yielded larger Cx43 clusters, of less regular shape, and larger Cx43-PKP2 subdomains. The Cx43-PKP2 subdomain was validated by a proximity ligation assay (PLA) and by Monte-Carlo simulations indicating an attraction between PKP2 and Cx43.
conclusions(i) Super-resolution fluorescence microscopy, complemented with Monte-Carlo simulations and PLAs, allows the study of the nanoscale organization of an interactome in cardiomyocytes. (ii) PKP2 and Cx43 share a common hub that permits direct physical interaction. Its relevance to excitability, electrical coupling, and arrhythmogenic right ventricular cardiomyopathy, is discussed.
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